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Blood, 15 March 2008, Vol. 111, No. 6, pp. 3266-3275. Prepublished online as a Blood First Edition Paper on September 7, 2007; DOI 10.1182/blood-2006-10-053801. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-10-053801v1 111/6/3266    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Xu, H. Articles by Ildstad, S. T. Search for Related Content PubMed PubMed Citation Articles by Xu, H. Articles by Ildstad, S. T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 24, 2006 Accepted July 27, 2007 Co-stimulatory blockade of CD154:CD40 in combination with T-cell lymphodepletion results in prevention of allogeneic sensitization Hong Xu, Jun Yan, Yiming Huang, Paula M. Chilton, Chuanlin Ding, Carrie L. Schanie, Li Wang, and Suzanne T. Ildstad* Institute for Cellular Therapeutics, University of Louisville, Louisville, KY, United States James Graham Brown Cancer Center, University of Louisville, Louisville, KY, United States * Corresponding author; email: stilds01{at}louisville.edu. Sensitization is a critical unresolved challenge in transplantation. We show for the first time that blockade of CD154 alone or combined with T-cell depletion prevents sensitization. Allogeneic skin grafts were rejected by recipients treated with anti--TCR, anti-CD154, anti-OX40L, or anti-ICOS mAb alone with a kinetic similar to untreated recipients. However, the production of anti-donor-MHC antibody was prevented in mice treated with anti-CD154 mAb only, suggesting a specific role for the CD154:CD40 pathway in B-cell activation. The impairment of T-cell-dependent B-cell responses by blocking CD154 occurs through inhibiting activation of T and B-cells and secretion of IFN- and IL-10. Combined treatment with both anti-CD154 and anti--TCR abrogated anti-donor antibody production and resulted in prolonged skin graft survival, suggesting the induction of both T- and B-cell tolerance with prevention of allogeneic sensitization. In addition, we show that the tolerance induced by combined treatment was nondeletional. Moreover, these sensitization-preventive strategies promote bone marrow engraftment in recipients previously exposed to donor alloantigen. These findings may be clinically relevant to prevent allosensitization with minimal toxicity and point to humoral immunity as playing a dominant role in alloreactivity in sensitized recipients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Xu, Y. Huang, P. M. Chilton, L.-R. Hussain, M. K. Tanner, J. Yan, and S. T. Ildstad Strategic Nonmyeloablative Conditioning: CD154:CD40 Costimulatory Blockade at Primary Bone Marrow Transplantation Promotes Engraftment for Secondary Bone Marrow Transplantation after Engraftment Failure J. Immunol., November 1, 2008; 181(9): 6616 - 6624. [Abstract] [Full Text] [PDF] H. Xu, J. Yan, and S. T. Ildstad Xenotransplantation: a step closer to reality? Blood, December 1, 2007; 110(12): 3815 - 3815. [Full Text] [PDF]

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